Since tumor promoters are nonmutagenic and active on the cell membrane, a hypothesis proposes that the biological response is mediated by specific promoter-induced changes in cell surface glycoconjugate targets. Recent investigations have led to the discovery of three promoter-sensitive glycoproteins in JB6 mouse epidermal cells, gp150, gp180, and gp220, having molecular weights of 150,000, 180,000 and 220,000, respectively. The gp180 and gp150 have been identified as the pro-alpha-1 and pro-alpha-2 subunits of procollagen, respectively. Both phorbol and non-phorbol promoters such as epidermal growth factor and mezerein are active in decreasing these three glycoproteins. 12-0-tetradecanoylphorbol-13-acetate (TPA) exposure switches off procollagen synthesis pretranslationally (probably transcriptionally) as indicated by a lack of translatable collagen mRNA. Antipromoting concentrations of retinoic acid prevent decreases in procollagen levels, but the retinoid action appears to be post-translational. We propose that the transcriptional switch affecting collagen synthesis indicates a required event in promotion coordinately regulated with procollagen.